Buprenorphine (BUP) is a high affinity partial (agonist that is not readily antagonized by opiate antagonists. BUP may therefore present an advantage over methadone as a treatment agent for opioid dependence because it may be possible to minimize or eliminate the delay between agonist and antagonist therapy. It may also be possible to administer both BUP and naltrexone simultaneously, providing a seamless transition from BUP to BUP-naltrexone to naltrexone. As an initial investigation of the feasibility of these transitions, BUP-naloxone interactions were examined at peak buprenorphine effects. After being stabilized on a maintenance dose of 8 mg/70 kg (n=1) or 16 mg/70 kg (n=8) of BUP every other day, opioid-dependent outpatients participated in challenge sessions every other week. Challenge sessions were conducted at Low (half maintenance), Medium (maintenance), and High (double maintenance) BUP doses, in either an ascending (n=4) or descending (n=5) sequence. One placebo and one active naloxone challenge session were conducted in random order at each condition. Subjects received 3 injections (i.m.) spaced 45 min apart during each challenge session. BUP was administered 150 min before the first injection. During active sessions, a saline placebo injection was followed by 3.0 mg/70 kg and 13 mg/70 kg doses of naloxone using a cumulative dosing procedure. All injections contained saline during placebo sessions. Dependent measures included an Adjective Withdrawal Scale, Visual analog Scale, Observer Ratings of opioid withdrawal and agonist effects, addiction Research Center Inventory, Digit-Symbol Substitution Test, vital signs, and pupil diameter. Physiological measures were collected every 5 min throughout the challenge session and all other measures were collected 15 and 30 min after each injection. Measures of precipitated withdrawal were directly related to naloxone dose across all Bup doses. Sequence dependent effects of Bup dose on precipitated withdrawal were also observed. Possible implications for the transition from agonist to antagonist therapy with buprenorphine will be discussed.